Trifluoroacetic acid → 5-Bromo-1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-one

HRID 1918896Notes

Reaction equation

HRID 1918896 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]3)[C:5](=[O:26])[N:4]([CH3:27])[CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][NH:14][CH2:13][CH2:12]3)[C:5](=[O:26])[N:4]([CH3:27])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58044031tert-Butyl 6-(6-bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 580437085-Bromo-1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-oneYield 68.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with 120a (1.14 g, 2.62 mmol), methylene chloride (10 mL) and trifluoroacetic acid (10 mL). The solution was stirred for 2 h at room temperature. After this time, the solution was concentrated under reduced pressure. The residue was partitioned between methylene chloride (100 mL) and 1 M aqueous dibasic potassium phosphate (30 mL). The aqueous layer was extracted with a 20% (v/v) solution of methanol in methylene chloride (3×100 mL). The organic extracts were combined, washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to afford a 68% yield (600 mg) of 153a as an off-white solid: mp 170-171° C.; 1H NMR (300 MHz, DMSO-d6) d 9.30 (s, 1H), 7.62 (m, 2H), 7.31 (s, 1H), 6.97 (d, 1H, J=7.8 Hz), 4.10 (br s, 1H), 3.83 (s, 2H), 3.43 (s, 3H), 2.96 (t, 2H, J=5.7 Hz), 2.68 (t, 2H, J=5.7 Hz); MS (ESI+) m/z 334.0 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
  2. customwas purged with nitrogen
  3. concentrationAfter this time, the solution was concentrated under reduced pressure
  4. customThe residue was partitioned between methylene chloride (100 mL) and 1 M aqueous dibasic potassium phosphate (30 mL)
  5. extractionThe aqueous layer was extracted with a 20% (v/v) solution of methanol in methylene chloride (3×100 mL)
  6. washwashed with brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. customThe drying agent was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-062b890e450f42eb80ecd1e08273db97
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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